Antimicrobial peptide Epinecidin-1 promotes complete skin regeneration of methicillin-resistant Staphylococcus aureus-infected burn wounds in a swine model

Abstract

This report shows that the antimicrobial peptide (AMP) Epinecidin-1 (Epi-1) efficiently heals MRSA-infected heat burn injuries and provides protection from infection in a pig model. The presence of an optimal level of Epi-1 induces cell proliferation by promoting cell cycle progression through an increase in S-phase cells. Epi-1 also induces proliferation to cover the wounded region in an in vitro cell proliferation assay using immortalized human epithelial HaCaT cells. Next, the in vivo wound healing efficiency of Epi-1 was tested in heat-burned pig skin infected with MRSA under in vivo conditions. Treatment of the injury with Epi-1 for 1 h at six hours post-infection completely healed the wound within 25 days. Conversely, the injury in the untreated control was not healed 25 days post-infection. Histological staining of wound sections with H&E showed that Epi-1 enhanced vascularization and increased epithelial activities in the wound region. Neutrophil recruitment to the wounded region in the Epi-1-treated sections was visualized by Giemsa staining. Additionally, Masson's trichrome staining of wound sections confirmed that Epi-1 enhanced extracellular collagen compound formation. The induction of sepsis-associated blood C-reactive protein (CRP) and the pro-inflammatory cytokine IL-6 in response to MRSA infection was also suppressed in pigs that received Epi-1. Taken together, the results demonstrate that the biomaterial Epi-1 heals wounds through increasing epithelial cell proliferation, vascularization, and the formation of collagen and controls MRSA infection-mediated sepsis in pigs.

Calcium-Dependent Calpain Activation-Mediated Mitochondrial Dysfunction and Oxidative Stress Are Required for Cytotoxicity of Epinecidin-1 in Human Synovial Sarcoma SW982 Cells

“…This property allows for selective killing of cancer cells by antimicrobial peptides. Exposure up to 11 µM did not cause cytotoxicity on human immortalized keratinocyte cell line HaCaT [34]. Additionally, epi-1 induces synovial sarcoma cell death by necrosis.…”

Peptides from Animal Origin: A Systematic Review on Biological Sources and Effects on Skin Wounds

“…The emergence of multidrug-resistant microorganisms stimulates an important challenge in regenerative medicine: the development of more efficient products to treat infected wounds [ 14 ]. Efficient antimicrobial products are also relevant since the colonization of wounds by microorganisms amplifies inflammation and oxidative tissue damage, slowing or inhibiting the progression of the healing process [ 12 , 26 , 34 ]. Thus, studies on the treatment of infected wounds are urgent, especially considering that controlling infection is essential to reduce the risk of developing chronic wounds [ 54 ].…”

Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds

“…Also the third wound healing stage can be supported by AMPs. SR-0379 promoted contraction capacity of human dermal fibroblast cells and accelerated in vivo wound healing by increasing collagen production (Tomioka et al, 2014 ) and Epi-1 enhanced the formation of collagen around the wound region (Huang et al, 2017 ). Other peptides can induce fibroblast-to-myofibroblast differentiation (Liu et al, 2014b ; Mu et al, 2014 ; Tang et al, 2014 ) which synthesize extracellular matrix components such as collagen (Gabbiani, 2003 ).…”

“…These peptides show the advantage of selectively enhancing host immune responses supporting the clearance of infection while on the contrary preventing overactivation of the immune system (Scott et al, 2007 ). Epi-1 recruited neutrophils to the wound site and decreased MRSA-induced inflammation and sepsis in heat wound-injured pigs, reflected in reduced IL-6 and C-reactive protein serum levels (Huang et al, 2017 ). For some immunomodulatory activities cell penetration of AMPs is required and can therefore particularly be provided by peptides that translocate not only into bacterial, but also into host cells (Mansour et al, 2015 ).…”